title: Smad2 and myocardin-related transcription factor B cooperatively regulate vascular smooth muscle differentiation from neural crest cells.
abstract: BACKGROUND
  Vascular smooth muscle cell (VSMC) differentiation from neural crest cells (NCCs) is critical for cardiovascular development, but the mechanisms remain largely unknown.
  
  
  OBJECTIVE
  Transforming growth factor-β (TGF-β) function in VSMC differentiation from NCCs is controversial. Therefore, we determined the role and mechanism of a TGF-β downstream signaling intermediate Smad2 in NCC differentiation to VSMCs.
  
  
  RESULTS
  By using Cre/loxP system, we generated a NCC tissue-specific Smad2 knockout mouse model and found that Smad2 deletion resulted in defective NCC differentiation to VSMCs in aortic arch arteries during embryonic development and caused vessel wall abnormality in adult carotid arteries where the VSMCs are derived from NCCs. The abnormalities included 1 layer of VSMCs missing in the media of the arteries with distorted and thinner elastic lamina, leading to a thinner vessel wall compared with wild-type vessel. Mechanistically, Smad2 interacted with myocardin-related transcription factor B (MRTFB) to regulate VSMC marker gene expression. Smad2 was required for TGF-β-induced MRTFB nuclear translocation, whereas MRTFB enhanced Smad2 binding to VSMC marker promoter. Furthermore, we found that Smad2, but not Smad3, was a progenitor-specific transcription factor mediating TGF-β-induced VSMC differentiation from NCCs. Smad2 also seemed to be involved in determining the physiological differences between NCC-derived and mesoderm-derived VSMCs.
  
  
  CONCLUSIONS
  Smad2 is an important factor in regulating progenitor-specific VSMC development and physiological differences between NCC-derived and mesoderm-derived VSMCs.
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.|School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Xie
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.|School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.
authors.forename: Ning
authors.initials: N
authors.lastname: Shi
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.
authors.forename: Junming
authors.initials: J
authors.lastname: Tang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ju
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California Ostrow School of Dentistry.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.|School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California Ostrow School of Dentistry.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA 30602.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities / Q000378:metabolism; D001665:Binding Sites; D002339:Carotid Arteries / Q000002:abnormalities / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000002:abnormalities / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009432:Neural Crest / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D051899:Smad2 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D014157:Transcription Factors; C503315:myocardin-related transcription factor B, mouse
keywords: Smad2; myocardin-related transcription factor B; neural crest; smooth muscle differentiation